Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications
Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/5/1394 |
| _version_ | 1797598677452193792 |
|---|---|
| author | Jan Miroslav Hartinger Danica Michaličková Eliška Dvořáčková Karolína Hronová Elke H. J. Krekels Barbora Szonowská Vladimíra Bednářová Hana Benáková Gabriela Kroneislová Jan Závora Vladimír Tesař Ondřej Slanař |
| author_facet | Jan Miroslav Hartinger Danica Michaličková Eliška Dvořáčková Karolína Hronová Elke H. J. Krekels Barbora Szonowská Vladimíra Bednářová Hana Benáková Gabriela Kroneislová Jan Závora Vladimír Tesař Ondřej Slanař |
| author_sort | Jan Miroslav Hartinger |
| collection | DOAJ |
| description | Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose. |
| first_indexed | 2024-03-11T03:24:27Z |
| format | Article |
| id | doaj.art-782c6215001449b6b728be4d3be716d0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:27Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-782c6215001449b6b728be4d3be716d02023-11-18T02:50:57ZengMDPI AGPharmaceutics1999-49232023-05-01155139410.3390/pharmaceutics15051394Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing ImplicationsJan Miroslav Hartinger0Danica Michaličková1Eliška Dvořáčková2Karolína Hronová3Elke H. J. Krekels4Barbora Szonowská5Vladimíra Bednářová6Hana Benáková7Gabriela Kroneislová8Jan Závora9Vladimír Tesař10Ondřej Slanař11Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDivision of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2311 EZ Leiden, The NetherlandsInternal Department of Strahov, General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech RepublicPeritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.https://www.mdpi.com/1999-4923/15/5/1394glycopeptidestherapeutic drug monitoringmethicillin resistant <i>Staphylococcus aureus</i> (MRSA)area under the curve (AUC)drug-exposurerenal replacement therapy |
| spellingShingle | Jan Miroslav Hartinger Danica Michaličková Eliška Dvořáčková Karolína Hronová Elke H. J. Krekels Barbora Szonowská Vladimíra Bednářová Hana Benáková Gabriela Kroneislová Jan Závora Vladimír Tesař Ondřej Slanař Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications Pharmaceutics glycopeptides therapeutic drug monitoring methicillin resistant <i>Staphylococcus aureus</i> (MRSA) area under the curve (AUC) drug-exposure renal replacement therapy |
| title | Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications |
| title_full | Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications |
| title_fullStr | Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications |
| title_full_unstemmed | Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications |
| title_short | Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications |
| title_sort | intraperitoneally administered vancomycin in patients with peritoneal dialysis associated peritonitis population pharmacokinetics and dosing implications |
| topic | glycopeptides therapeutic drug monitoring methicillin resistant <i>Staphylococcus aureus</i> (MRSA) area under the curve (AUC) drug-exposure renal replacement therapy |
| url | https://www.mdpi.com/1999-4923/15/5/1394 |
| work_keys_str_mv | AT janmiroslavhartinger intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT danicamichalickova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT eliskadvorackova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT karolinahronova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT elkehjkrekels intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT barboraszonowska intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT vladimirabednarova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT hanabenakova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT gabrielakroneislova intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT janzavora intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT vladimirtesar intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications AT ondrejslanar intraperitoneallyadministeredvancomycininpatientswithperitonealdialysisassociatedperitonitispopulationpharmacokineticsanddosingimplications |